Method of preparing diphenyl acetic acid



United States Patent METHOD OF PREPARIhig DIPHENYL ACETIC GeorgeKesslin, New York, N. Y., assignor to Kay-Fries Chemicals, Inc., WestHaverstraw, N. Y., a corporation of New York No Drawing. ApplicationSeptember 28, 1951, Serial No. 248,881

6 Claims. (Cl. 260-515) This invention relates to improvements inmethods of preparing diphenyl acetic acid, and, more particularly, to aone-step method employing glyoxylic acid as a starting material. Thisapplication is a continuation-in-part of my prior application, Ser. No.137,033, filed January 5, 1950, for Method of Preparing Diphenyl AceticAcid, now abandoned, which application is a division of the prior jointapplication of Herbert Elkinton, George Kesslin, and Leonard Nicholl,Serial No. 92,968, filed May 12, 1949, for Methods of Preparing DiphenylAcetic Acid, now Patent No. 2,517,856, of August 8, 1950, for Method ofPreparing Diphenyl Acetic Acid.

Diphenyl acetic acid is an important intermediate or starting compoundfor the preparation of a number of special chemicals having particularutility as bacteriostats in the treatment of malaria and like diseases.

The present application is directed to the process of forming diphenylacetic acid, directly in a one-step treatment, by reacting benzene withglyoxylic acid or its hydrate, in the presence of chlorsulfonic acid asa catalyst.

It is, therefore, among the features of novelty and advantage of thepresent invention to provide a novel method for the preparation ofdiphenyl acetic acid by the direct reaction of glyoxylic acid, or itshydrate, and benzene, in the presence of chlorsulfonic acid as acatalyst.

In the process herein, glyoxylic acid hydrate is the equivalent ofglyoxylic acid for the preparation of diphenyl acetic acid.

In carrying out the process herein, one mol of glyoxylic acid, or itshydrate, is reacted directly with two mols of benzene, in the presenceof an excess of benzene as a solvent, using chlorsulfonic acid as acatalyst, according to the following equation:

I Cl\ /0 H0 0 O 8 0 1 C O OH O (ISCsHu) (Glyoxyllc) (Benzene)(Ohlorsulfonic acid acid) Gil-coon no1+ rnso.

Patented July 24, 1956 phenyl acetic acid in aqueous solution. Theaqueous solution of the sodium salt separates out from the benzene as aseparate layer. The aqueous diphenyl acetic acid sodium salt layer isseparated from the washed benzene layer, and is then acidified to reformthe diphenyl acetic acid, which precipitates out of solution. Theseparated diphenyl acetic acid is then recovered and purified in theusual manner.

The following example, using glyoxylic acid hydrate as a startingmaterial, is illustrative of the process herein:

Materials "ice 18.6 gms. glyoxylic acid hydrate 162.0 gms. chlorsulfonicacid 200 cc. benzene Procedure The chlorsulfonic acid was added, withagitation, to the mixture of benzene and glyoxylic acid hydrate at areaction temperature of 2030 C., over a 2-hr. period. Agitation was thencontinued at the same temperature for 1 /2 hrs. longer. The reactiontemperature was then raised to 50 C., and kept there for one hourlonger. The entire reaction mixture was then quenched in 1000 cc. ofcold water, and the excess benzene removed by distillation. The aqueousacid solution was then decanted from the gummy crude, and the crude wastaken up into solution with a mixture of 20 gms. of NaOI-I in 300 cc. ofH20. After the crude dissolved as the sodium salt, the solution wasextracted with cc. of toluene. The residual aqueous solution was thentreated with permanganate and carbon treated to improve the color of theproduct. The diphenyl acetic acid was then precipitated out of thesolution by adding concentrated sulfuric acid to a red test on alkalitest paper. The product was then filtered and dried in the oven at C.

Results Weight of dried crude diphenyl acetic acid 31 gms. (analyzing93.2%

by titration). Theory 43.0 gms. diphenyl acetic acid. Yield 67.2% oftheory.

By two recrystallizations from toluene, there was obtained 5.5 gms. of aproduct with a melting point of 14l.5-143.5 C., and analyzing 100%diphenyl acetic acid by titration.

A mixed melting point determination with pure diphenyl acetic acidshowed no depression of the melting point142.0 C.144.5 C.

It will now be appreciated that there has been disclosed a novel methodfor the direct preparation of diphenyl acetic acid from glyoxylic acidand its hydrate, by reaction with benzene in the presence ofchlorsulfonic acid as a catalyst, and without requiring the use ofintermediate solvents or treating steps.

What is claimed is:

1. The method of preparing diphenyl acetic acid, in a single step,comprising reacting one mol of glyoxylic acid and two mols of benzene,in an excess of benzene as a solvent, and in the presence of a catalystconsisting of chlorsulfonic acid whereby to form diphenyl acetic acid.

2. The method of preparing diphenyl acetic acid in a single step,comprising reacting one mol of glyoxylic acid and two mols of benzene,in an excess of benzene, and in the presence of chlorsulfonic acid as acatalyst to form diphenyl acetic acid dissolved in the excess of benzeneand a subjacent layer of sulfuric acid, decanting the diphenyl aceticacid-benzene layer, washing with caustic solution to form an aqueoussolution of an alkali salt of diphenyl acetic acid and a supernatantwashed benzene layer, separating the aqueous caustic diphenyl aceticacid layer, and acidifying, whereby to precipitate diphenyl acetic acid.

3. The improved method of preparing diphenyl acetic acid comprisingreacting glyoxylic acid and benzene in the presence of chlorsulfonicacid as a catalyst.

4. The improved method of preparing diphenyl acetic acid comprisingreacting glyoxylic acid and benzene, in reactive amounts, at roomtemperature, in the presence of chlorsulfonic acid as a catalyst.

5. The improved method of preparing dip'nenyl acetic acid comprisingreacting one mol of glyoxylic acid hydrate and two mols of benzene, atroom temperature, in an excess of benzene, and in the presence ofchlorsulfonic acid as a catalyst.

6. The improved method of preparing diphenyl acetic acid comprisingpreparing a bath of one mol of glyoxylic acid hydrate and two mols ofbenzene, in an excess of benzene, adding catalytic amounts ofchlorsulfonic acid, at room temperature, and over a two-hour period, tothe reaction bath; agitating the bath for one and one-half r J 4 hourslonger; raising the reaction temperature to C., and heatinga't' thistemperature for one hour.

References Cited in the file of this patent UNITED STATES PATENTSElkinton et a1. Aug. 8, 1950 'OTHER REFERENCES Boettiger: Archiv derPharm., vol. 233, pp. 111 to 118 (1895).

Ostromisslenski: Ber. Deut. Chem., vol. 41, pp. 3029 to 34 (1908).

Rueggeberg et al.: Ind. and Eng. Chem., vol. 38, pp. 211-14 (1946).

Rueggeberg et al.: Ind. and Eng. Chem, vol. 39, pp. 868 (1947).

Rueggeberg et al.: Ind. and Eng. Chem, vol. 39, page 1683 (1947).

Vieles et al.: pp. 247 to 51.

Bull. Soc. Chim. de France, vol. 1947,

1. THE METHOD OF PREPARING DIPHENYL ACETIC ACID, IN A SINGLE STEP,COMPRISING REACTING ONE MOL OF GLYOXYLIC ACID AND TWO MOLS OF BENZENE,IN AN EXCESS OF BENZENE AS A SOLVENT, AND IN THE PRESENCE OF A CATALYSTCONSISTING OF CHLORSULFONIC ACID WHEREBY TO FORM DIPHENYL ACETIC ACID.